Abstract
Purpose The purpose of this study was to examine the association between baseline serum gamma-glutamyl transferase (GGT) and incident diabetes mellitus and to explore their dose-response relationship in a cohort of Japanese adults. Patients and Methods. Data were drawn from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study between 2004 and 2015, including hierarchical information on participants ≥18 years of age without diabetes mellitus, preexisting diabetes mellitus, heavy alcohol drinking, or other liver diseases (e.g., hepatitis B/C). The final analytic sample included 15464 participants, 373 of who were diagnosed as diabetes mellitus with a maximum 13-year follow-up. The risk of incident diabetes mellitus according to baseline serum GGT was estimated using multivariable Cox proportional hazards models and a two-piecewise linear regression model was developed to find out the threshold effect. Results Being in the highest quintile versus the lowest quintile of GGT levels was associated with an almost twofold increased risk of incident diabetes mellitus (hazard ratio 1.83 (95% CI 1.06, 3.15)), independent of age, gender, smoking status, alcohol intake, BMI, SBP, triglycerides, fatty liver, ALT, AST, and fasting plasma glucose. Further analysis revealed a positive curvilinear association between GGT and incident diabetes mellitus, with a saturation effect predicted at 24 IU/L. When serum GGT level was less than 24 IU/L, the risk of developing diabetes mellitus increased significantly with an increase in serum GGT levels (HR 1.04 (1.02, 1.07), P=0.0017). Besides, the association was more significant in nonsmoking participants than ex- or current-smokers (P=0.0017). Besides, the association was more significant in nonsmoking participants than ex- or current-smokers (P for interaction = 0.0378). Conclusion Serum GGT level was a significant predictor of subsequent risk of diabetes mellitus, which increased by 4% for every 1 IU/L increase in GGT when GGT was less than 24 IU/L.
Highlights
According to the International Diabetes Federation, the global number of patients with type 2 diabetes (T2DM) has increased unprecedentedly [1]
Serum Gamma-glutamyl transferase (GGT) level is directly proportional to Body mass index (BMI), waist circumference, fatty liver, ALT, AST, total cholesterol, triglyceride, HbA1c, and fasting plasma glucose levels, while inversely proportional to HDL-cholesterol levels
We further revealed a nonlinear relationship between serum GGT levels and risk of diabetes mellitus
Summary
According to the International Diabetes Federation, the global number of patients with type 2 diabetes (T2DM) has increased unprecedentedly [1]. As the most common chronic disease, diabetes mellitus causes huge socioeconomic pressures on both patients and healthcare systems [2]. It is, important to fully understand risk factors for diabetes mellitus, which can be used to prevent and screen diabetes mellitus. Gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) are often used as biomarkers for liver function [3]. GGT is a transferase that catalyzes the transfer of gammaglutamyl functional groups from glutathione to other acceptors to regulate the redox status and may be a marker of oxidative stress [4], which plays a role in the pathogenesis of T2DM [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
